The introduction of cloned nucleotide sequences into animal cells has greatly facilitated the study of the control and function of various eucaryotic genes. Bacterial-animal cell shuttle vectors, capable of selection and amplification as plasmids in bacteria and as episomal or integrated genetic elements in animal cells, are particularly convenient for this purpose. Such vectors require genes capable of conferring a selective advantage on both bacteria and animal cells harboring them. It is often the animal cell side of this requirement which is particularly difficult to meet, since, ideally, selection and amplification should be possible in many types of cells.
Up until now, the most commonly used systems used for these purposes were the neo genes selectable with the antibiotic G-418, the gpt gene selectable with mycophenolic acid, and the dhfr gene selectable with methotrexate. However, important drawbacks have been noted for each of these systems. Thus, neo and gpt cannot be amplified, dhfr is easily amplified but difficult to select in anything but dhfr.sup.- recipients, and all of the markers require the use of mutagenic drugs for selection.
Therefore, a selectable marker for shuttle vectors possessing both efficient dominant animal cell transfection as well as strong amplification capabilities would be highly desirable.